Sandbox PgpWWC
From Proteopedia
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== Function and Expression == | == Function and Expression == | ||
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ABCB1 functions to expel xenotoxins from the body into bile, urine, and the intestinal lumen.<ref name="Marchetti"> | ABCB1 functions to expel xenotoxins from the body into bile, urine, and the intestinal lumen.<ref name="Marchetti"> | ||
function | function | ||
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== Structure == | == Structure == | ||
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ABCB1 is located in the cellular membrane, adopting an inward-facing "V-shaped" structure. Since the hydrophobic substrates are hydrophobic and can partition into the lipid bilayer, research suggests that substrate enters ABCB1 through two portals within the lipid bilayer.<ref name="Aller" /> When a substrate binds to the binding site, a conformational change causes the protein to open to the outside of the cell, releasing the substrate. ATP is then hydrolyzed to re-induce the inward-facing conformation in preparation for the binding of another substrate compound from the bilayer.<ref>Chufan, E. E., Sim, H. M., & Ambudkar, S. V. (2014). Chapter Three – Molecular Basis of the Polyspecificity of P-Glycoprotein (ABCB1): Recent Biochemical and Structural Studies. Advances in Cancer Research, 125, 71-96.</ref> This efflux of substrate out of the cell prevents the accumulation of potentially toxic xenobiotics; however, this effective expulsion of a wide variety of substrates causes the multi-drug resistance. | ABCB1 is located in the cellular membrane, adopting an inward-facing "V-shaped" structure. Since the hydrophobic substrates are hydrophobic and can partition into the lipid bilayer, research suggests that substrate enters ABCB1 through two portals within the lipid bilayer.<ref name="Aller" /> When a substrate binds to the binding site, a conformational change causes the protein to open to the outside of the cell, releasing the substrate. ATP is then hydrolyzed to re-induce the inward-facing conformation in preparation for the binding of another substrate compound from the bilayer.<ref>Chufan, E. E., Sim, H. M., & Ambudkar, S. V. (2014). Chapter Three – Molecular Basis of the Polyspecificity of P-Glycoprotein (ABCB1): Recent Biochemical and Structural Studies. Advances in Cancer Research, 125, 71-96.</ref> This efflux of substrate out of the cell prevents the accumulation of potentially toxic xenobiotics; however, this effective expulsion of a wide variety of substrates causes the multi-drug resistance. | ||
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== Clinical Relevance == | == Clinical Relevance == | ||
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As mentioned previously, ABCB1 is located in the liver, kidney, adrenal gland, intestine, BBB, placenta, blood-testis barrier, and blood-ovarian barriers. Furthermore, ABCB1 is overexpressed in tumor cells. The presence of of ABCB1 in these locations prevents the entry of toxins into the cells, but also prevents the accumulation of therapeutic drugs. For the BBB, this protein prevents the entry of many psychotherapeutic drugs. | As mentioned previously, ABCB1 is located in the liver, kidney, adrenal gland, intestine, BBB, placenta, blood-testis barrier, and blood-ovarian barriers. Furthermore, ABCB1 is overexpressed in tumor cells. The presence of of ABCB1 in these locations prevents the entry of toxins into the cells, but also prevents the accumulation of therapeutic drugs. For the BBB, this protein prevents the entry of many psychotherapeutic drugs. | ||
Revision as of 15:42, 29 April 2015
P-glycoprotein (ABCB1)
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References
- ↑ 1.0 1.1 Aller SG, Yu J, Ward A, Weng Y, Chittaboina S, Zhuo R, Harrell PM, Trinh YT, Zhang Q, Urbatsch IL, Chang G. Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science. 2009 Mar 27;323(5922):1718-22. PMID:19325113 doi:323/5922/1718
- ↑ He L, Liu GQ. Effects of various principles from Chinese herbal medicine on rhodamine123 accumulation in brain capillary endothelial cells. Acta Pharmacol Sin. 2002 Jul;23(7):591-6. PMID:12100750
- ↑ 3.0 3.1 Marchetti S, Mazzanti R, Beijnen JH, Schellens JH. Concise review: Clinical relevance of drug drug and herb drug interactions mediated by the ABC transporter ABCB1 (MDR1, P-glycoprotein). Oncologist. 2007 Aug;12(8):927-41. PMID:17766652 doi:http://dx.doi.org/10.1634/theoncologist.12-8-927
